Volume 17, Number 11,
Issue of June 1, 1997
pp. 4382-4388
Copyright ©1997 Society for Neuroscience
Paradoxical Effects of External Modulation of Inhibitory
Interneurons
Received Oct. 24, 1996; revised Jan. 24, 1997; accepted March 10, 1997.
Misha V. Tsodyks1, 2, 3,
William E. Skaggs2,
Terrence J. Sejnowski3, 4, and
Bruce L. McNaughton2
1 Department of Neurobiology, Weizmann
Institute, Rehovot 76100, Israel, 2 Arizona Research
Laboratories, Division of Neural Systems, Memory and Aging, University
of Arizona, Tucson, Arizona 85724, 3 Howard Hughes Medical
Institute, Computational Neurobiology Laboratory, The Salk Institute
for Biological Studies, La Jolla, California 92037, and
4 Department of Biology, University of California at San
Diego, La Jolla, California 92093
The neocortex, hippocampus, and several other brain regions contain
populations of excitatory principal cells with recurrent connections
and strong interactions with local inhibitory interneurons. To improve
our understanding of the interactions among these cell types, we
modeled the dynamic behavior of this type of network, including
external inputs. A surprising finding was that increasing the direct
external inhibitory input to the inhibitory interneurons, without
directly affecting any other part of the network, can, in some
circumstances, cause the interneurons to increase their firing rates.
The main prerequisite for this paradoxical response to external input
is that the recurrent connections among the excitatory cells are strong
enough to make the excitatory network unstable when feedback inhibition
is removed. Because this requirement is met in the neocortex and
several regions of the hippocampus, these observations have important
implications for understanding the responses of interneurons to a
variety of pharmacological and electrical manipulations. The analysis
can be extended to a scenario with periodically varying external input,
where it predicts a systematic relationship between the phase shift and depth of modulation for each interneuron. This prediction was tested by
recording from interneurons in the CA1 region of the rat hippocampus
in vivo, and the results broadly confirmed the model. These
findings have further implications for the function of inhibitory and
neuromodulatory circuits, which can be tested experimentally.
Key words:
network model;
hippocampus;
oscillation;
theta rhythm;
inhibition;
interneurons
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